The potential of aptamers for cancer research.

Aptamers are promising alternatives to antibodies and can be used as high affinity agents for the cancer detection and the targeted drug transportation. In this manuscript, we highlight the advantages of aptamers, such as high affinities, specificity and excellent chemical stabilities, which are likely to benefit for the diagnosis of cancer in its early stages and then achieve molecular-level treatment. Also, we discuss the challenges and problems in the current application of aptamers.

Synthesis of cell composite alginate microfibers by microfluidics with the application potential of small diameter vascular grafts.

Fabrication of small diameter vascular grafts (SDVGs) with appropriate responses for clinical application is still challenging. In the present work, the production and characterization of solid alginate based microfibers as potential SDVG candidates through the method of microfluidics were considered original. A simple glass microfluidic device with a 'L-shape' cylindrical-flow channel in the microfluidic platform was developed. The gelation of microfibers occurred when the alginate solution and a CaCl2 solution were introduced as a core flow and as a sheath flow, respectively. The diameters of the microfibers could be controlled by varying the flow rates and the glass capillary tubes diameters at their tips. The generated microfibers had somewhat rough and porous surfaces, their suture retention strengths were comparable to the strength of other tissue engineered grafts. The encapsulated mesenchymal stem cells proliferated well in the microfibers, and showed a stable endothelialization under the angiogenesis effects of vascular endothelial growth factor and fibroblastic growth factor. The in vivo implant into the mice abdomens indicated that cell composite microfibers caused a mild host reaction. These encouraging results suggest great promise of the application of microfluidics as a future alternative in SDVGs engineering.

Milling Positive Master for Polydimethylsiloxane Microfluidic Devices: The Microfabrication and Roughness Issues.

We provide a facile and low-cost method (F-L) to fabricate a two-dimensional positive master using a milling technique for polydimethylsiloxane (PDMS)-based microchannel molding. This method comprises the following steps: (1) a positive microscale master of the geometry is milled on to an acrylic block; (2) pre-cured PDMS is used to mold the microscale positive master; (3) the PDMS plate is peeled off from the master and punctured with a blunt needle; and (4) the PDMS plate is O2 plasma bonded to a glass slide. Using this technique, we can fabricate microchannels with very simple protocols quickly and inexpensively. This method also avoids breakage of the end mill (ϕ = 0.4 mm) of the computerized numerical control (CNC) system when fabricating the narrow channels (width < 50 µm). The prominent surface roughness of the milled bottom-layer could be overcomed by pre-cured PDMS with size trade-off in design. Finally, emulsion formation successfully demonstrates the validity of the proposed fabrication protocol. This work represents an important step toward the use of a milling technique for PDMS-based microfabrication.

Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication.

Newcastle disease virus (NDV) can replicate in tumor cells and induce apoptosis in late stages of infection. However, the interaction between NDV and cells in early stages of infection is not well understood. Here, we report that, shortly after infection, NDV triggers the formation of autophagosomes in U251 glioma cells, as demonstrated by an increased number of double-membrane vesicles, GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) a dot formations, and elevated production of LC3II. Moreover, modulation of NDV-induced autophagy by rapamycin, chloroquine or small interfering RNAs targeting the genes critical for autophagosome formation (Atg5 and Beclin-1) affects virus production, indicating that autophagy may be utilized by NDV to facilitate its own production. Furthermore, the class III phosphatidylinositol 3-kinase (PI3K)/Beclin-1 pathway plays a role in NDV-induced autophagy and virus production. Collectively, our data provide a unique example of a paramyxovirus that uses autophagy to enhance its production.

Avian reovirus triggers autophagy in primary chicken fibroblast cells and Vero cells to promote virus production.

Avian reovirus (ARV) is an important cause of disease in poultry. Although ARV is known to induce apoptosis in infected cells, the interaction between ARV and its target cells requires further elucidation. In this report, we show that the ARV isolate strain GX/2010/1 induces autophagy in both Vero and primary chicken embryonic fibroblast (CEF) cells based on the appearance of an increased number of double-membrane vesicles, the presence of GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) dot formation, and the elevated production of LC3II. We further demonstrate that the class I phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway contributes to autophagic induction by ARV infection. Moreover, treatment of ARV-infected cells with the autophagy inducer rapamycin increased viral yields, while inhibition of the autophagosomal pathway using chloroquine led to a decrease in virus production. Altogether, our studies strongly suggest that autophagy may play a critical role in determining viral yield during ARV infection.

Newcastle disease virus induces apoptosis in cisplatin-resistant human lung adenocarcinoma A549 cells in vitro and in vivo.

Cisplatin (DDP) is widely used in lung cancer chemotherapy. However, cisplatin resistance represents a major obstacle in effective clinical treatment. This study aims to investigate whether Newcastle disease virus (NDV) exhibits an oncolytic effect on cisplatin-resistant A549 lung cancer cells. We found that NDV induced A549/DDP cell apoptosis via the caspase pathway, particularly involving caspase-9, while the mitogen-activated protein kinase (MAPK) and Akt pathways also contributed to apoptotic induction. Furthermore, NDV displayed oncolytic effects in a mouse A549/DDP lung cancer model. Collectively, our data indicate that NDV could overcome the cisplatin resistance in lung cancer cells in vitro and in vivo.